Rheometer and method for the use thereof

ABSTRACT

A device for determining the rheological properties of blood may include a channel having at least one channel sub-section that has a substantially constant cross-section; apparatus for determining a pressure differential along at least a portion of the sub-section of the channel; a first reservoir that is adapted to be located at a first end of the channel and to be placed in fluid communication with the channel, the first reservoir being of variable internal volume; a second reservoir that is adapted to be placed in fluid communication with first reservoir via the channel, the second reservoir being of variable internal volume; means for allowing blood to be introduced into the device; an outlet for allowing gas to be expelled from the device; and means for varying the volume of the first reservoir.

This application is a continuation of U.S. patent application Ser. No.16/346,854, filed May 1, 2019 and now issued as U.S. Pat. No. 11,378,507B2, which is a national stage entry under 35 U.S.C. § 371 ofInternational Application No. PCT/GB2017/053393, filed Nov. 10, 2017,which claims the benefit of GB Application No. 1619337.7, filed Nov. 15,2016, the entire content of all being incorporated herein by reference.

TECHNICAL FIELD

The present disclosure relates to a device for determining therheological properties of non-Newtonian fluids, in particular to adevice for determining the rheological properties of blood, and to amethod for the use thereof.

BACKGROUND

It is often desirable to obtain a rapid evaluation of the rheologicalproperties of a patient's blood. Knowledge of such rheologicalproperties is of value in assessing the administration of coagulants andanticoagulants to patients. It may also predict the likelihood of ableed or thrombotic event in those that have a propensity to bleed orare at increased risk of clotting. Further situations in which it isimportant to know the rheological properties of blood include monitoringpatients during surgery and during the reversal of anti-coagulationfollowing surgery. Changes in blood rheology also occur in patients withsepsis and may provide an early indication that the condition ispresent. If sepsis is detected sufficiently early, treatment for thecondition may be relatively straightforward.

Similarly, during the administration of anti-coagulants or the reversalof blood anti-coagulation following surgery, it would be very useful tohave access to timely feedback on changes in the rheological propertiesof blood.

However, current tests for determining the rheological properties ofblood tend to be time-consuming and require that a volume of blood iswithdrawn from the patient and sent to a specialist bench-mountedinstrument, such as a thromboelastograph, for analysis. Thus, there is aneed for a simple bedside instrument that can be used more routinely.

In the following description the term blood encompasses and refers tohuman blood and to animal blood and can also mean blood and bloodproducts.

SUMMARY

The present disclosure may provide a device for determining therheological properties of blood, the device comprising two reservoirs,each having a variable internal volume and being adapted to be placed influid communication with the other via a channel. Blood may be caused toflow along the channel by altering the internal volumes of the tworeservoirs. The channel includes one or more sections each having asubstantially uniform cross section. Where there are two or more uniformsections each section differs in cross sectional area from othersections. The device is provided with a pressure gauge or pressuresensors for determining a pressure differential along at least a portionof the channel that has a substantially uniform cross-section.

Information about the rheology of the liquid blood may be obtained bydetermining the pressure differentials across a number of sections ofdiffering cross-sectional area resulting from a given flow rate.Alternatively, information about the rheology of the blood may beobtained by determining the pressure differential across a section ofsubstantially uniform cross section at a number of different definedflow rates.

Thus, the device is based on a simple, alternating direction pumpingsystem that does not require large volumes of blood in order to be ableto function. Other pumping systems used in previous devices such as thatdescribed in WO 2011/051706 are less advantageous. For example,peristaltic pumping systems may damage suspended components in theliquid (e.g. the blood cells present in a blood sample) through thecompression of the tube containing the liquid. Centrifugal pumpingsystems are not practicable for small volumes of liquid. Additionally,flow rates from a centrifugal or peristaltic pump may be difficult tomonitor, leading to the need for an additional component (a flowmeter)within the device. The flow rate from a reservoir having a variableinternal volume is accurately determined by its rate of change involume.

The device of the present disclosure allows liquid to be pumped inalternating directions along the channel, such that certain artefacts inthe measurements, due for example to slight non-uniformities in thetubing, will tend to cancel each other out. Pumping liquid inalternating directions may allow more complex analyses to be performed,such as the measurement of the oscillatory fluid response withproperties such as the viscous and elastic moduli.

In a first aspect, the present disclosure may provide a device fordetermining the rheological properties of a non-Newtonian fluid, such asblood, the device comprising:

-   -   a channel having at least one channel sub-section that has a        substantially constant cross-section;    -   apparatus for determining a pressure differential along at least        a portion of the sub-section of the channel;    -   a first reservoir that is adapted to be located at a first end        of the channel and to be placed in fluid communication with the        channel, the first reservoir being of variable internal volume;    -   a second reservoir that is adapted to be placed in fluid        communication with first reservoir via the channel, the second        reservoir being of variable internal volume;    -   means for allowing blood to be introduced into the device;    -   an outlet for allowing gas to be expelled from the device; and    -   means for varying the volume of the first reservoir, such that        when the first and second reservoirs are in fluid communication        with the first and second ends of the channel respectively,        blood may be caused to flow along the channel in alternating        directions.

The at least one channel sub-section may be straight or curved.

In a second aspect, the present disclosure may provide a device fordetermining the rheological properties of blood, the device comprising:

-   -   a channel having at least one channel sub-section that has an        increasing or decreasing cross-section, preferably a uniformly        increasing or decreasing cross-section;    -   apparatus for determining a pressure differential along at least        a portion of the sub-section of the channel;    -   a first reservoir that is adapted to be located at a first end        of the channel and to be placed in fluid communication with the        channel, the first reservoir being of variable internal volume;    -   a second reservoir that is adapted to be placed in fluid        communication with first reservoir via the channel, the second        reservoir being of variable internal volume;    -   means for allowing blood to be introduced into the device;    -   an outlet for allowing gas to be expelled from the device; and    -   means for varying the volume of the first reservoir, such that        when the first and second reservoirs are in fluid communication        with the first and second ends of the channel respectively,        blood may be caused to flow along the channel in alternating        directions.

The at least one channel sub-section may be straight or curved.

The at least one channel sub-section may have a cross-section thatincreases or decreases in a non-uniform manner, for example, thecross-section may increase in a semi-hyperbolic manner or followsinusoidal variations.

Thus in both the first and second aspects of the disclosure, when thefirst and second reservoirs are in fluid communication with each othervia the channel, blood may be caused to flow in either direction alongthe channel by altering the internal volume of the first and/or secondreservoir. Both the first and second aspect take the same approach toproviding a device that can measure the rheological properties of blood.For the device according to the second aspect of the present disclosurealternating flow through such a non uniform channel can furnishadditional information on the elastic properties of a viscoelastic fluidsuch as blood. Such tapered sections can all taper in the same directionwithin a channel or some can taper in opposing directions.

Typically, in the device according to the first or second aspect of thepresent disclosure the first reservoir is a syringe, that is, itcomprises a plunger and a hollow cylinder, the plunger being movablealong the longitudinal axis of the cylinder to alter the internal volumeof the reservoir. The syringe may be used to obtain a blood sample froma patient and may subsequently be placed in fluid communication with thechannel. In this case, the syringe provides the means for allowingliquid to be introduced into the device. After testing, the syringe maybe removed from the device to allow the blood sample to be used in othertests.

Typically, the device also comprises means for varying the volume of thesecond reservoir, such that when the first and second reservoirs are influid communication with each other, fluid may be caused to flow alongthe channel by varying the volume of the second reservoir. Typically,the second reservoir is also a syringe.

In other embodiments, the reservoir may be provided by a flexiblecasing, e.g. an elastic bulb.

In certain embodiments, the second reservoir comprises compressibleportions located internally so as to provide the reservoir with avariable internal volume. The compressible portions may be, for example,air pockets or resiliently-deformable inserts.

In general, the channel of the device according to the first aspect ofthe disclosure has a plurality of sub-sections, each sub-section havinga substantially constant cross-section and being provided with arespective differential pressure apparatus for determining a pressuredifferential across at least a portion of that sub-section, thesub-sections being of different cross-sections.

In this case, rheological properties of the liquid may be determinedfrom the pressure readings obtained from the plurality of sub-sections.Each sub-section determines an apparent viscosity, which for anon-Newtonian fluid such as blood, will differ from sub-section tosub-section. The rheological properties may be derived from therelationship between the apparent viscosity and the strain rate in eachof the sub-sections.

In the event that the alternating flow is not a simple forward andreverse flow, rheological properties related to the viscosity, such asan apparent complex modulus, may be derived by relating the transientpressure to the transient flowrate.

In the case that only one sub-section is present, it may be necessary tocarry out tests at different flow rates in order to determine therheological properties of the blood. Different flow rates producedifferent strain rates, and hence for non-Newtonian fluids, differentapparent viscosities. Thus, rheological properties of the liquid may bedetermined from the relationship between the apparent viscosity and thestrain rate.

The apparatus for determining a differential pressure may be a pressuremonitoring system. The pressure monitoring system may be electronicallyor physically monitored for real time or subsequent processing andanalysis. For example, the pressure sensors may be piezo-resistivestrain gauges or may be capacitive sensors sensing the deformity of thechannels through which the fluid flows.

In the case that more than one sub-section is provided, the sub-sectionsmay all be aligned with each other. The channel may be made ofdisposable plastic tubing incorporating the requisite sections. Thetubing may be rigid or flexible. It may be fitted into a straight outerchannel into which it can be easily inserted and from which it can beeasily removed. Alternatively, a lower plate may be provided with achannel formed in its upper surface into which the plastic tubing of thechannel can be fitted and then clamped in place, for example, by anupper or supplementary plate. The plastic tubing may be formed as anintegral part of the upper plate, with pressure sensors incorporatedinto the lower plate. In this way the upper plate, through which bloodpasses, may be an inexpensive disposable part, with the more expensive,non disposable portion including sensors and electrical componentsincorporated into the lower plate. This may help to provide a morecompact device. Overall, care should be taken in the design to avoidsharp changes in direction that could damage or trap the fluid.

Typically, the internal diameter of the at least one sub-section isgreater than 150 mm, preferably greater than 200 micron, more preferablygreater than 300 micron. Typically, the internal diameter of the atleast one sub-section is less than 3000 micron, preferably less than2000 micron, more preferably less than 1000 micron.

Preferably, the at least one sub-section has a circular cross-section.

Typically, the length of the at least one sub-section is greater than0.5 cm, preferably greater than 1 cm. Typically, the length of the atleast one sub-section is less than 30 cm, preferably less than 15 cm,more preferably less than 10 cm.

Typically, the ratio of length to internal diameter of the at least onesub-section is greater than 5:1, preferably greater than 10:1, morepreferably greater than 20:1.

Typically, the distance between the first and second reservoirs, whenthey are in fluid communication with each other via the channel, is lessthan 30 cm, preferably less than 20 cm.

Typically, the first and second reservoirs each have a maximum volumethat is less than 50 ml, preferably less than 40 ml, more preferablyless than 30 ml. Preferably a standard syringe size of 1 ml, 3 ml, 5 ml,10 ml, 20 ml or 30 ml is used.

In certain embodiments, the device according to the first or secondaspects of the disclosure may comprise means for imposing apre-determined flow rate on the blood (that is, the device may functionas a strain-controlled rheometer). In other embodiments, the deviceaccording to the first or second aspects of the disclosure may comprisemeans for imposing a pre-determined pressure differential on the blood(that is, the device may function as a stress-controlled rheometer).

In a third aspect, the present disclosure may provide a device fordetermining the rheological properties of blood, the device comprising:

-   -   a channel;    -   an apparatus for determining a pressure differential along at        least a portion of the channel;    -   a first reservoir that is adapted to be located at a first end        of the channel and to be placed in fluid communication with the        channel, the first reservoir being of variable internal volume;    -   a second reservoir that is adapted to be placed in fluid        communication with first reservoir via the channel, the second        reservoir being configured to hold a liquid received from the        channel, such that the liquid may be returned to the channel;    -   means for allowing blood to be introduced into the device;    -   an outlet for allowing gas to be expelled from the device; and    -   means for varying the volume of the first reservoir, such that        when the first and second reservoirs are in fluid communication        with the first and second ends of the channel respectively,        blood may be caused to flow along the channel in alternating        directions.

The channel may have one or more of the features of the channel of thedevice according to the first or second aspects of the disclosure.

The first reservoir may have one or more of the features of the firstreservoir of the device according to the first or second aspects of thedisclosure.

In a fourth aspect, the present disclosure may provide a method ofmeasuring the rheological properties of blood, comprising the steps of:

-   -   providing a device according to the first aspect of the        disclosure;    -   introducing blood into the device;    -   expelling gas or fluid from the device;    -   ensuring that the first and second reservoirs are in fluid        communication with the channel;    -   altering the internal volume of the first reservoir so as to        cause blood to flow along the channel in a first direction,        between the first and second reservoirs;    -   recording or measuring the rate of blood flow between the first        and second reservoirs; and    -   monitoring the apparatus for determining a pressure differential        along at least a portion of the at least one sub-section having        substantially uniform cross section; and    -   causing the blood to flow along the channel in a second        direction.

In general, the method comprises the step of causing liquid to flowalong the channel in a second direction. By taking measurements in bothflow directions and averaging them (or using more advanced signalprocessing techniques such as Fourier Transforms or FFT), it may bepossible to reduce measurement errors and/or reduce the need for precisemounting of the device on a stable surface.

The method may be carried out e.g. by imposing a known flow rate on theblood and monitoring the associated pressure differential.Alternatively, the method may be carried out by imposing a knownpressure differential and measuring the associated flow rate.

Preferably, the blood is made to cycle a plurality of times between thefirst and second reservoirs. Forward and reverse flow cycles may beundertaken for a small number of cycles to measure the rheologicalproperties of the fluid at a defined point in time, or may be continuedfor a protracted period, in order to monitor changes in rheologicalbehaviour, for example, due to clotting or gelling of the fluid.

In the case that the channel has a plurality of sub-sections each havinga respective cross section different from the other sub-sections,testing may be carried out at a constant flow rate or a periodic flowwith a single amplitude and frequency.

In the case the that channel has a single sub-section, it may benecessary to carry out tests at different flow rates in order to imposedifferent strain rates on the test liquid. Alternatively, if it is onlydesired to monitor the progress of clotting or gelling of the testliquid, the flow rate may be held constant or may be the same insuccessive cycles.

The liquid may be a blood sample. In this case, the method may comprisethe step of providing a syringe containing a blood sample, and placingthe syringe in fluid communication with the channel such that thesyringe functions as the first reservoir. In this way, the step oftransferring the blood sample from the syringe to a separate reservoirprovided by the measurement device may be avoided, thus reducing thelevel of skill required to operate the device, as well as the delay intesting the sample.

Preferably, the method includes the step of calibrating the device. Thisis typically done through the steps of:

-   -   introducing a Newtonian fluid of known viscosity (for example,        water) into the device;    -   expelling gas from the device;    -   ensuring that the first and second reservoirs are in fluid        communication with each other via the channel;    -   altering the internal volume of the first reservoir so as to        cause liquid to flow along the channel in a first direction,        between the first and second reservoirs; and    -   monitoring the pressure apparatus to determine the pressure        difference along the least one sub-section.

Calibration of the device using a Newtonian fluid of known viscosity mayallow the device to be manufactured to less exacting engineeringtolerances. That is, the requirement for precision engineering of thedevice is reduced, since the rheological properties of the blood sample(which can be used as a test liquid) may be calculated in relation tothe known properties of the calibration fluid, rather than beingcalculated directly from the dimensions of the device. Thus the apparentviscosity of the blood can be calculated from the following formulawhich does not include explicit reference to the tube diameter or thedistance between the pressure sensor points:μ/μ_(C) =ΔPG _(C)/(ΔP _(C) G)

In the above formula, μ is (apparent) viscosity, G is volumetric flowrate, and ΔP is pressure difference. Subscript ‘C’ refers to theNewtonian calibration liquid. Typically, the step of calibrating thedevice comprises causing the calibration liquid to cycle repeatedly fromthe first reservoir to the second reservoir and back.

It is preferable that the volume discharged at each stroke is less thanthe complete volume of the reservoir because discharging the final 10%to 20% of the volume places the red blood cells under stress that maycause them to rupture causing haemolysis. The stress arises both fromthe high strain rates caused by the high radial velocities and by theplunger closing against the end of the syringe. The radial velocitiesoccur when the blood at the circumference of the piston is driven to theaxis, where the streamlines turn through 90 degrees for the blood toexit through the axially located tubing or channel. Then when theplunger end of the syringe strikes the end of the syringe body itdirectly crushes any red cells remaining in the reservoir.

In one embodiment the internal volume is reduces by not more than 80%within the first 10 seconds. Higher discharge rates may damage liquidssuch as blood.

In certain cases blood is caused to flow in alternating directions alongthe channel for at least 5 minutes. This may allow changes in therheology of the blood to be monitored, such as those caused by clotting.Typically, the period of each individual flow cycle is in the range1-120 s, preferably in the range 10-120 s.

The device used in the method according to the fourth aspect of thedisclosure may have one or more of the optional features of the deviceaccording to the first or second aspect of the disclosure, whether takenalone or in combination.

BRIEF DESCRIPTION OF THE DRAWINGS

The disclosure will now be described by way of example with reference tothe following Figures.

FIG. 1 shows a schematic plan view of a device for determining therheological properties of blood, according to an embodiment of the firstaspect of the disclosure.

FIG. 2 shows a schematic plan view of a device for determining therheological properties of blood including a channel that alternates indirection, according to another embodiment of the first aspect of thedisclosure.

DETAILED DESCRIPTION

Referring to FIG. 1 , a block 30 comprises a plurality of channels 21,22, 23, each channel having a circular internal cross-section. Eachchannel 21, 22, 23 has a different internal diameter in the range200-2000 micron. The channels are each 1-15 cm in length and have alength:internal diameter ratio in the range 10:1 to 40:1. The channelsare arranged in series so as to provide a fluid flow path betweenopposite ends of block 30. Each channel is provided with means ofmonitoring the respective pressure differentials. In the illustratedembodiment each channel is provided with tappings for a respectivedifferential pressure gauge 41, 42, 43.

A first syringe 11 comprises a plunger 11 a and a hollow cylinder 11 band a hollow connector 11 c. The plunger is movable along a longitudinalaxis of the cylinder. The connector is aligned with the longitudinalaxis of the cylinder and is in fluid communication with the cylinder.

The connector 11 c is reversibly engaged with channel 21, so as toprovide a fluid flow path between the cylinder and channel 21. Thus theplunger 11 a is movable relative to cylinder 11 b, connector 11 c, andblock 30.

A second syringe 12 comprises a plunger 12 a, a hollow cylinder 12 b anda hollow connector 12 c that is reversibly engaged with hollow cylinder12 b. The plunger is movable along a longitudinal axis of the cylinder.The connector is aligned with the longitudinal axis of the cylinder andis in fluid communication with the cylinder.

The connector 12 c is engaged with channel 23 and provides a fluid flowpath between channel 23 and cylinder 12 b. Thus, plunger 12 a is movablerelative to cylinder 12 b, connector 12 c and block 30.

The first and second syringes each have an internal volume of about 5-20ml.

Driving element 31 has an elongate central portion 31 a and side arms 31b, 31 c extending laterally from each end of the central portion. Sidearm 31 b is configured to urge against plunger 11 a of the firstsyringe, while side arm 31 c is configured urge against plunger 12 a ofthe second syringe. Driving element 31 is electronically controlled.

In use, first syringe 11 is provided with a sample of a Newtonian liquidof known viscosity, which is held within the hollow cylinder 11 b. Theconnector 11 c is brought into engagement with channel 21 so as toprovide a fluid flow path from the hollow cylinder 11 b to channel 21.Hollow cylinder 11 b is then clamped into place relative to block 30.

The second syringe 12 is arranged such that the plunger 12 a is fullydepressed and connector 12 c is temporarily disengaged from cylinder 12b.

Side arm 31 b is urged against plunger 11 a so as to cause the liquid toflow out of cylinder 11 b and through hollow connector 11 c, channels21, 22, 23 and hollow connector 12 c. Any gas present within the firstand second syringes and channels 21, 22, 23 is expelled via hollowconnector 12 c of the second syringe, after which hollow cylinder 12 bis re-engaged with hollow connector 12 c and clamped into place.

Driving element 31 is then activated so as to urge side arm 31 a furtheragainst plunger 11 a of the first syringe 11. This causes the liquid tobe discharged from syringe 11 and forced through channels 21, 22, 23 sothat the second syringe 12 becomes charged with the liquid.Consequently, the internal volume of the second syringe increases andplunger 12 a is urged away from block 30.

The pressure drop across each channel 21, 22, 23 is measured during themotion. When syringe 11 is fully discharged, the motion of drivingelement 31 is reversed and pressure drop measurements are taken withflow in the opposite direction. The velocity of movement in bothdirections is accurately controlled and recorded. The velocity is thesame in both directions. The cycle is repeated a sufficient number oftimes to ensure that accurate and reproducible pressure drop readingsare recorded. These measurements are calibration measurements. They canbe taken immediately before tests on blood or can be undertaken atinitial assembly so that each block 30 is pre-calibrated.

In use, a cycle similar to the calibration cycle is undertaken, butusing a blood sample in syringe 11. The forward and reverse flow cyclemay be undertaken for a small number of cycles to measure the initialrheological properties of the blood, or may be continued for aprotracted period (for example, up to half an hour) to track changes inthe rheological properties of the blood as it clots.

It is advisable to maintain the device at a fixed orientation during use(for example, block 30 may extend in a generally horizontal direction ora generally vertical direction). This will help to reduce potentialinaccuracies arising from changes in the pressure exerted by the weightof the liquid itself. However, due to the relatively small amount ofliquid in the device, it is not anticipated that these effects will bevery significant.

The device is either maintained at an accurately controlled temperatureor insulated to maintain a substantially constant temperature, which ismeasured. This allows the results to be corrected for the variation ofrheological properties with temperature.

In the embodiment shown in FIG. 1 , the channels 21, 22, 23 are allaligned along the same axis. However, in other embodiments the channelsmay be arranged such that liquid flowing along a pair of adjacentchannels initially travels generally in a direction from the firstsyringe towards the second syringe, but changes course at the junctionbetween the adjacent channels so as to travel generally in a directionfrom the second syringe towards the first syringe. Such configurationsmay allow a more compact device to be provided. This is illustrated inFIG. 2 .

In the embodiment shown in FIG. 1 , the channels 21, 22, 23 are formedwithin block 30. However, other embodiments are envisaged in which thechannels are provided by tubes of different diameters or by a singletube having sections of different diameter. Tapered tubes are alsoenvisaged.

It should be emphasised that although FIG. 1 shows a device having threechannels, other embodiments are possible that have a greater or lessernumber of channels. The present disclosure does not require that thechannels be placed in any particular sequence in terms of their internaldiameters. A mechanically simpler embodiment requires just a singlechannel having a substantially constant cross-section. In this case,differing strain rates are achieved by altering the forward and backwardvelocity of the driving element 31 from cycle to cycle.

The connecting tubes between the syringes and the block may be replacedby a direct connection such as a standard Luer lock thereby simplifyingthe set up and reducing the volume of blood between the syringe and theblock.

In the embodiment shown in FIG. 2 an alternative arrangement is shownincorporating a channel that alternates in direction in order to reducethe maximum linear dimension of the device. The operation and use of thearrangement shown in FIG. 2 is as for the embodiment shown in FIG. 1 andas for the calibration cycle described above, in which the sectionscorresponding to FIG. 1 are numbered on and incremented by 100.

Therefore referring to FIG. 2 , a block 130 comprises a plurality ofchannels 121, 122, 123, each channel having a circular internalcross-section. Each channel 121, 122, 123 has a different internaldiameter in the range 200-2000 micron. The channels are each 1-15 cm inlength and have a length:internal diameter ratio in the range 10:1 to40:1. The channels are arranged in series in a snake like arrangement soas to provide a fluid flow path between opposite ends of block 130 witha reduction in the linear extent of the device. Each channel is providedwith means of monitoring the respective pressure differentials. In theillustrated embodiment each channel is provided with tappings for arespective differential pressure gauge 141, 142, 143.

A first syringe 111 comprises a plunger 111 a and a hollow cylinder 111b and a hollow connector 111 c. The plunger in the same way as in thearrangement shown in FIG. 1 , is movable along a longitudinal axis ofthe cylinder. The connector is aligned with the longitudinal axis of thecylinder and is in fluid communication with the cylinder.

The connector 111 c is reversibly engaged with channel 121, so as toprovide a fluid flow path between the cylinder and channel 121. Thus theplunger 111 a is movable relative to cylinder 111 b, connector 111 c,and block 130.

A second syringe 112 comprises a plunger 112 a, a hollow cylinder 112 band a hollow connector 112 c that is reversibly engaged with hollowcylinder 112 b. The plunger is movable along a longitudinal axis of thecylinder. The connector is aligned with the longitudinal axis of thecylinder and is in fluid communication with the cylinder.

The connector 112 c is engaged with channel 123 and provides a fluidflow path between channel 123 and cylinder 112 b. Thus, plunger 112 a ismovable relative to cylinder 112 b, connector 112 c and block 130.

The first and second syringes each have an internal volume of about 5-20ml.

Driving element 131 has an elongate central portion 131 a and side arms131 b, 131 c extending laterally from each end of the central portion.Side arm 131 b is configured to urge against plunger 111 a of the firstsyringe, while side arm 131 c is configured urge against plunger 112 aof the second syringe. Driving element 131 is electronically controlled.

In use, the calibration and operation functions of the first syringe 111and the second syringe 112 is as set out for the device according to thefirst aspect of the present disclosure with syringe 11 and 12.

It may also be advantageous for the embodiments of both FIG. 1 and FIG.2 to divide the instrument through the plane of the channel, so that allsensors, electrical and electromechanical parts are in one section, alower section or portion. The other section of the division, the upperportion or section, may consist of tubing that is slotted into channelsof semi-circular cross section and clamped in place. Alternately, theupper section may consist of a plate incorporating channels (or tubing)of circular cross section that slot into channels of semi circular crosssection incorporated in the lower section. The upper section may bedisposable after use. In either of these alternatives, pressure sensorsin the lower section may sense the pressure in the tubing or channelwithout contacting the fluid. As a further alternative, pressure sensorsmay be incorporated in tubing with electrical connections to the lowersection.

Various modifications may be made to the described embodiment withoutdeparting from the scope of the present disclosure, for example otheralternatives and options may be envisaged within the scope of theclaims, for example the driving element 31 may be replaced by a clamp onthe plunger 11 a so that the plunger is driven in and withdrawn at oneend. The plunger 12 a then moves back and forth in response to thepressure in the fluid exerted on the plunger.

The flow actuator and pressure monitoring apparatus or monitoring systemmay be connected to an electronic system for processing the signals andrecording and/or displaying relevant rheological information, such asthe projected gelling or clotting time.

The structure and orientation of the apparatus may be of an alternativedesign and shaping, there may be any number of sections. The sectionsmay be of any shape or structure through which blood or a test fluidcould flow. For example, each section could have a uniformcross-sectional area, could have a steadily changing cross-sectionalarea, or could have a varying cross-sectional area. The number ofsections may be varied, in the examples provided there are threesections, however more or less than three sections can also beenvisaged. The number of component parts may be varied, in the example,the block containing the channel is illustrated as one component.However, it is preferably divided into sub-components so that theblood-contacting channel is an inexpensive disposable part, whilst thesensing components are not so readily disposable. For example, thechannel may be a disposable plastic tube that fits in the channelillustrated in the figures. The block may also divide in the planeillustrated in the figure to provide easy exchange of the disposablepart. The apparatus may comprise any suitable material, or combinationof materials, of construction.

What is claimed is:
 1. A device for determining rheological propertiesof a non-Newtonian fluid, the device comprising: a channel, the channelhaving a plurality of sub-sections, each sub-section having asubstantially constant cross-section being provided with a respectivedifferential pressure apparatus for determining a pressure differentialacross at least a portion of that sub-section, the sub-sections being ofdifferent cross-sectional areas; a first reservoir that is adapted to belocated at a first end of the channel and to be placed in fluidcommunication with the channel, the first reservoir being of variableinternal volume; a second reservoir that is adapted to be placed influid communication with first reservoir via the channel, the secondreservoir being of variable internal volume; an inlet for allowing fluidto be introduced into the device; an outlet, separate to the inlet, atan end of the channel for allowing gas to be substantially eliminatedfrom the device; and an electronically controlled driving element forvarying the volume of the first reservoir, such that when the first andsecond reservoirs are in fluid communication with the first and secondends of the channel respectively, varying the volume of the firstreservoir causes fluid to flow along the channel in alternatingdirections, at pre-determined flow rates in each of the channelsub-sections such that pre-determined strain rates are imposed on thefluid.
 2. The device of claim 1, wherein an internal diameter of the atleast one sub-section is in a range of 200-2000 micron.
 3. The device ofclaim 1, wherein a length of the at least one sub-section is in a rangeof 1-15 cm.
 4. The device of claim 1, wherein the first and secondreservoirs each have a maximum volume that is less than 50 ml.
 5. Thedevice of claim 1, wherein one or both of the first and secondreservoirs comprises a plunger and a hollow cylinder, the plunger beingmovable along a longitudinal axis of the cylinder to alter the internalvolume of the reservoir.
 6. The device of claim 5, wherein one or bothof the first and second reservoirs is provided by a syringe.
 7. Thedevice of claim 1, wherein one or both of the first and secondreservoirs is provided by an elastic body.
 8. The device of claim 1,wherein the device comprises a first section including electromechanicalparts and associated electronics, and a second section comprisingportions for introducing and handling fluid in the device.
 9. The deviceof claim 8, wherein the second section of the device is above, below,within or adjacent the first section and is disposable.
 10. A method ofmeasuring the rheological properties of blood, the method comprising:providing a device according to claim 1; introducing non-Newtonian fluidinto the device; substantially eliminating gas from the device; ensuringthat the first and second reservoirs are in fluid communication with thechannel; altering the internal volume of the first reservoir so as tocause fluid to flow along the channel in a first direction, between thefirst and second reservoirs at pre-determined flow rates in each of thechannel sub-sections such that pre-determined strain rates are imposedon the fluid; recording or measuring a rate of fluid flow between thefirst and second reservoirs; monitoring the apparatus for determining apressure differential along at least a portion of the at least onesub-section having substantially uniform cross-section; and causing thefluid to flow along the channel in a second direction.
 11. The method ofclaim 10, comprising cycling the fluid a plurality of times between thefirst and second reservoirs.
 12. The method of claim 10, furthercomprising: tracking changes in rheological behaviour of the fluid asthe fluid gels or clots.
 13. The method of claim 10, comprising takingmeasurements in both flow directions and averaging the measurements. 14.The method of claim 10 wherein recording or measuring the rate of fluidflow between the first and second reservoirs comprises using FourierTransfer, or FFT, signal processing.
 15. The method of claim 10, furthercomprising one of maintaining the device at a controlled temperature orinsulating the device to maintain a substantially constant temperature.